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Nat Biomed Eng. 2019 May;3(5):392-401. doi: 10.1038/s41551-019-0372-9. Epub 2019 Mar 25.

Rapid volumetric optoacoustic imaging of neural dynamics across the mouse brain.

Gottschalk S1, Degtyaruk O1, Mc Larney B1,2, Rebling J1,2,3,4,5,6, Hutter MA1,7, Deán-Ben XL1,3,4,5,6, Shoham S8,9,10, Razansky D11,12,13,14,15,16.

Author information

1
Institute for Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany.
2
Faculty of Medicine, Technical University of Munich, Munich, Germany.
3
Faculty of Medicine, University of Zurich, Zurich, Switzerland.
4
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
5
Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland.
6
Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland.
7
Department of Electrical and Computer Engineering, Technical University of Munich, Munich, Germany.
8
Tech4Health Institute, New York University Langone Health, New York, NY, USA.
9
Neuroscience Institute, New York University Langone Health, New York, NY, USA.
10
Department of Ophthalmology, New York University Langone Health, New York, NY, USA.
11
Institute for Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany. daniel.razansky@uzh.ch.
12
Faculty of Medicine, Technical University of Munich, Munich, Germany. daniel.razansky@uzh.ch.
13
Faculty of Medicine, University of Zurich, Zurich, Switzerland. daniel.razansky@uzh.ch.
14
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. daniel.razansky@uzh.ch.
15
Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland. daniel.razansky@uzh.ch.
16
Department of Information Technology and Electrical Engineering, ETH Zurich, Zurich, Switzerland. daniel.razansky@uzh.ch.

Abstract

Efforts to scale neuroimaging towards the direct visualization of mammalian brain-wide neuronal activity have faced major challenges. Although high-resolution optical imaging of the whole brain in small animals has been achieved ex vivo, the real-time and direct monitoring of large-scale neuronal activity remains difficult, owing to the performance gap between localized, largely invasive, optical microscopy of rapid, cellular-resolved neuronal activity and whole-brain macroscopy of slow haemodynamics and metabolism. Here, we demonstrate both ex vivo and non-invasive in vivo functional optoacoustic (OA) neuroimaging of mice expressing the genetically encoded calcium indicator GCaMP6f. The approach offers rapid, high-resolution three-dimensional snapshots of whole-brain neuronal activity maps using single OA excitations, and of stimulus-evoked slow haemodynamics and fast calcium activity in the presence of strong haemoglobin background absorption. By providing direct neuroimaging at depths and spatiotemporal resolutions superior to optical fluorescence imaging, functional OA neuroimaging bridges the gap between functional microscopy and whole-brain macroscopy.

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